Suspension of vitamin c in alcohol



United States Patent SUSPENSION OF VITAMIN C IN ALCOHOL SOLUTION 0F VITAMIN K Ernest B. McQuarrie, Concord, Califl, assignor to Cutter Laboratories, Berkeley, Calif., a corporation of Caliorma No Drawing. Application September 24, 1956 Serial No. 611,751

3 Claims. (Cl. 167--81) This invention relates to and in general has for its object the provision of a preparation of two normally incompatible vitamins and to a method for producing such preparation.

It is now well known and accepted that both vitamin K and vitamin C are necessary or valuable for enhancing the rapid and safe recovery of patients undergoing surgery or suffering from gastrointestinal bleeding. Vitamin K, probably in the form of vitamin K is required for most animals and man for the hepatic synthesis of prothrombin, a necessary component of the blood clotting mechanism. Most postsurgical patients who are in poor nutritional state or who have received bishydroxycoumarin (Dicumarol) or another similar anticoagulation drug do not have sufficient stored vitamin K to insure proper blood clotting. Similarly, patients suffering from prolonged bouts of gastrointestinal bleeding are depleted of vitamin K. In such cases, the parenteral administration of vitamin K, preferably as vitamin K is necessary to insure against the occurrence of uncontrollable or excess bleeding. Vitamin C is the only vitamin which has been demonstrated to be required for adequate wound healing in man. Since many postsurgical patients and most patients suffering from gastrointestinal bleeding are in poor nutritional state, the administration of vitamin C, preferably parenterally, is necessary for proper convalescence.

Inasmuch as the indication and route of administration for both vitamins is often the same, it is obviously desirable to provide them in the same container in a ready-to-use form. However, the preparation of such a mixture has been considered either impossible or impractical in the past inasmuch as the two drugs are incompatible. This is due to the fact that vitamin K is rapidly inactivated by reducing agents (vitamin C is a strong reducing agent), and vitamin C is inactivated by oxidizing agents such as vitamin K. A preparation which could be prepared economically and which would contain these two vitamins in a sterile stable form would be both unique and of great utility to the medical profession.

More specifically then, the object of this invention is the provision of a compatible admixture of vitamin K and vitamin C in a stable form.

A further object of this invention is the provision of a preparation of the character above described which when added to intravenous infusion solutions such as saline, glucose, fructose, amino acids, etc., is suitable and efficacious in the treatment of postsurgical patients and patients suffering from gastrointestinal bleeding.

Still another object of this invention is the provision of a vitamin preparation including a salt of ascorbic acid suspended in an alcohol solution of vitamin K Exemplary of the method by which such a preparation can be made are the two following examples.

Example 1 6 grams of vitamin K and 2.5 grams of sorbitan monooleate (Tween 80) are dissolved in 400 ml. of U.S.P.

2,879,205 Patented Mar. 24, 1959 absolute ethanol under an atmosphere of anhydrous nitrogen. To this is added 60 grams of dry, finely powdered (325 mesh is convenient) sodium ascorbate and sufiicient U.S.P. absolute ethanol to bring the volume to 500 ml. The mixture is then agitated sufliciently to insure a uniform suspension. 5.3 ml. aliquots are then filled into amber glass ampules and sealed in the usual manner. The sealed ampules are then heat sterilized in any conventional manner. These ampules can be stored for subsequent infusion into a bottle of intravenous injection fluid. The administration of this hottle of fluid will provide therapeutically etiective doses of both vitamins K and vitamin C.

Example 2 6 grams of vitamin K are dissolved in 400 m1. of a solution comprising 40 percent propylene glycol and 60 percent absolute ethanol under an atmosphere of anhydrous nitrogen. To this is added 60 grams of dry finely powdered calcium ascorbate and sufiicient of the propylene glycol-ethanol mixture to make a final volume of 500 ml. After agitation to provide a uniform suspension. 5.3 ml. aliquots are filled into amber ampules, sealed and sterilized. These are then used as indicated in Example l.

95 percent ethanol can be used in place of absolute ethanol but at some sacrifice in stability.

in these two examples, the specific proportions of vita min K and vitamin C set forth are not critical and are chosen to give the dosages of the two vitamins desired in the end product, that is, the amounts required to produce the desired physiological effect. Aside from this, the vitamin K can be added to the limit of its solubility in alcohol, and the sodium ascorbate can be added up to the point where the resulting suspension would be too thick to readily pass through an injection needle.

Vitamin K is a specific fat soluble vitamin K, otherwise known as phytonadione (U.S.P), and although only this member of the vitamin K group has been set forth in the two examples above given, other fat soluble members of the vitamin K group can be substituted for vitamin K for their chemical and physical characteristics are very similar to vitamin K However, it should here be observed that these other members are not commonly available, and, furthermore, they are not of much medical importance.

Although in the two specific examples above set forth, only the sodium and calcium salts of ascorbic acid have been used, any water soluble salt of ascorbic acid which is insoluble in alcohol, nontoxic, and which is substantially physiologically active as ascorbic acid can be used. For example, the potassium, ammonium, and magnesium salts will serve just as well as the sodium and calcium salts, although they are not currently commercially available.

The vitamin K is dissolved in alcohol under anhydrous nitrogen simply for the purpose of excluding as much oxygen and moisture as possible. Except for availability and cost, any other similar inert gas will serve the purpose.

The sorbitan monooleate (Tween is used as a conventional dispersing agent to aid in the dispersion of the vitamin K when the suspension is added to an aqueous intravenous solution just prior to use.

As a substitute for the propylene glycol-ethanol mixture referred to in Example 2, any other similar polyhydroxyalcoholethanol mixture which will be nontoxic and which will dissolve sufiicient vitamin K, to produce the desired therapeutic results can be used.

Basically, my method may be considered as a mechanism for bringing two mutually incompatible vitamins into intimate admixture, but at the same time insulating one from the other. The reason for this, of course, is that although the vitamin K is in solution, it cannot react with the vitamin C which is merely in suspension.

Actually, no chemical reaction takes place during the process unless dissolving the K in its solvent can be considered as such a reaction.

I claim:

1. A vitamin preparation comprising: a suspension of a salt of ascorbic acid in an alcohol solution of phytonadione, said salt being selected from the group consisting of sodium ascorbate, potassium ascorbate, calcium ascorbate, ammonium ascorbate, and magnesium ascorbate, and said alcohol being selected from the group consisting of ethanol and propylene glycol.

2. The method of preparation of a vitamin preparation comprising: dissolving phytonadione in an alcohol under an inert gas and adding a salt of ascorbic acid to the resulting solution, said alcohol being selected from the group consisting of ethanol and propylene glycol, and said salt being selected from the group consisting of sodium ascorbate, calcium ascorbate, potassium ascorbate, ammonium ascorbate and magnesium ascorbate.

3. An intravenous media containing a vitamin prep- References Cited in the file of this patent UNITED STATES PATENTS 2,721,161 Maiese Oct. 18, 1955 FOREIGN PATENTS 619,065 Great Britain Mar. 3, 1949 OTHER REFERENCES Drug and Cos. Ind., vol. 7, No. 4, page 489, April 1952.

Bandelin: J. Am. Pharm. Assoc., April 1955, sci. ed., pp. 241-244.

Pratt: J. Amer. Pharm. Assoc., March 1950, vol. 39, pp. 127-134.

Physicians Desk Reference, Medical Economics, Rutherford, NJ. 8th ed., 1954, pp. 445, 459, 570. 

1. A VITAMIN PREPARATION COMPRISING: A SUSPENSION OF A SALT OF ASCORBIC ACID IN AN ALCOHOL SOLUTION OF PHYTONADIONE, SAID SALT BEING SELECTED FROM THE GROUP CONSISTING OF SODIUM ASCORBIC, POTASSIUM ASCORBIC, CALCIUM ASCORBATE AMMONIUM ASCORBATE AND MAGENSIUN ASCORBOBATE, AND SAID ALCOHOL BEING SELECTED FROM THE GROUP CONSISTING OF ETHANOL AND PROPYLENE GLYCOL 